Live combined Bacillus subtilis and Enterococcus faecium improves glucose and lipid metabolism in type 2 diabetic mice with circadian rhythm disruption via the SCFAs/GPR43/GLP-1 pathway
HAN Ruimin
ZHAO Manke
YUAN Junfang
SHI Zhenhong
WANG Zhen
WANG Defeng
Abstract：Objective To investigate the effects of live combined Bacillus subtilis and Enterococcus faecium(LCBE)on glucose and lipid metabolism in mice with type 2 diabetes mellitus(T2DM)and circadian rhythm disorder(CRD)and explore the possible mechanisms.Methods KM mice were randomized into normal diet(ND)group(n=8),high-fat diet(HFD)group(n=8),and rhythm-intervention with HFD group(n=16).After 8 weeks of feeding,the mice were given an intraperitoneal injection of streptozotocin(100 mg/kg)to induce T2DM.The mice in CRD-T2DM group were further randomized into two equal groups for treatment with LCBE(225 mg/kg)or saline by gavage;the mice in ND and HFD groups also received saline gavage for 8 weeks.Blood glucose level of the mice was measured using a glucometer,and serum levels of Bmal1,PER2,insulin,C-peptide and lipids were determined with ELISA.Colon morphology and hepatic lipid metabolism of the mice were examined using HE staining and Oil Red O staining,respectively,and fecal short-chain fatty acids(SCFAs)was detected using LC-MS;GPR43 and GLP-1 expression levels were analyzed using RT-qPCR and Western blotting.Results Compared with those in CRD-T2DM group,the LCBE-treated mice exhibited significant body weight loss,lowered levels of PER2,insulin,C-peptide,total cholesterol(TC)and LDL-C,and increased levels of Bmal1 and HDL-C levels.LCBE treatment significantly increased SCFAs,upregulated GPR43 and GLP-1 expressions at both the mRNA and protein levels,and improved hepatic steatosis and colon histology.Conclusion LCBE ameliorates lipid metabolism disorder in CRD-T2DM mice by reducing body weight and improving lipid profiles and circadian regulators possibly via the SCFAs/GPR43/GLP-1 pathway.
Keywords：type 2 diabetes mellituscircadian rhythmlive combined Bacillus subtilis and Enterococcus faeciumshort-chain fatty acidsglucolipid metabolism
Publication Date：2025-07-20
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：8( 1490-1497 )